P.20 
AUG 29 '94 13:53 VUMC CELL BIOLOGY 
PRINCIPAL INVESTIGATOR: Jeffrey Holt MD Page 2 
TITLE OF PROPOSAL: Antisense Retrovirus Gene Therapy for Metastatic 
Breast Cancer 
We plan to inject the vector (with its antisense gene) into fluid that is building up in 
your [lungs, abdomen, brain] and that contain breast cancer cells. We do not expect normal 
cells in your body either to die or even to be injured because the vector targets breast cells 
and the only breast cells in this region of your body are cancer cells. 
Procedures to be followed: 
You will be admitted to the Clinical Research Center where you will have a complete 
physical exam, blood, and urine tests to determine your overall health. The amount of blood 
drawn from you will be no more than a tablespoon at any one time, and will be less than one 
pint over the entire treatment period. At this time you will have a chest X-ray and a 
electrocardiogram. Additional tests may be required depending on your state of health and 
prior treatments. You will also have a pregnancy test if you are less than 55 years of age. A 
CT scan will be done to assess the amount that your breast cancer has spread into your body 
fluid. A CT scan produces similar pictures but uses X-rays. The type of scan done will depend 
on your prior therapy and the extent of your cancer. Each scan takes about 60-90 minutes. 
We plan on you spending four days in the Clinical Research Center for the initial 4 
infusions of virus vector. Each day we will draw a s imil ar, small blood sample from a vein in 
your arm which will be used for tests to ensure that there is no spreading of the virus into the 
blood We will also place a needle into your body to remove the fluid which contains breast 
cancer cells and to infuse the vector into the fluid where the cancer is located. Fluids which 
contain cancer cells are found generally in one of three places: the peritoneum which is the 
lining or the belly surrounding the intestines, the pleura which is the lining of the chest 
surrounding the lungs, and the cerebrospinal fluid which is the fluid which surrounds the 
brain and spinal cord. We will withdraw fluid from the site where your cancer cells are 
present, and infuse virus vector for each of the four days that you are in the Clinical Research 
Center. The fluid which is removed will be analyzed to determine: 
1. The percentage of cancer cells which are taking up the vector/gene combination 
2. The number of cancer cells present in the fluid 
3. Whether cancer cells are being killed by the therapy 
While you are in the Clinical Research Center you will be continuously monitored, and 
will have an EKG. After the four day period in the Clinical Research Center you will be 
discharged, but will be asked to return at day 7 for a blood sample and a fluid sample. On day 
14 you will be asked to return for a blood sample, fluid sample, and an MRI or CAT scan to 
assess whether there has been a significant change in your breast cancer. This treatment in no 
way interferes with other treatment options for your cancer. After completion of the vector 
infusions, you may immediately start chemotherapy, radiation, pleurodesis, etc, depending 
upon the recommendation of your cancer specialist. Because this is experimental research, we 
expect to follow you for a long time to determine the long term effects of this treatment, and 
will request an autopsy when you die. 
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